Phospholipase D: its role in metabolism processes and disease development

Abstract

Phospholipase D (PLD) is one of the key enzymes that catalyzes the hydrolysis of cell membrane phospholipids. In this review current knowledge about six human PLD isoforms, their structure and role in physiological and pathological processes is summarized. Comparative analysis of PLD isoforms structure is presented. The mechanism of the hydrolysis and transphosphatidylation performed by PLD is described. The PLD1 and PLD2 role in the pathogenesis of some cancer, infectious, thrombotic and neurodegenerative diseases is analyzed. The prospects of PLD isoform-selective inhibitors development are shown in the context of the clinical usage and the already-existing inhibitors are characterized. Moreover, the formation of phosphatidylethanol (PEth), the alcohol abuse biomarker, as the result of PLD-catalyzed phospholipid transphosphatidylation is considered.

Curbing Lipids: Impacts ON Cancer and Viral Infection

“…Phospholipase D (isoenzymes PLD1 and PLD2) catalyzes the hydrolysis of cell membrane phospholipids and plays the role in several cancers and infectious diseases [146]. PLD inhibitors have been proposed as novel compounds for the treatment of cancers, neurodegenerative disorders, and viral infections [147].…”

Blockade of PLD1 potentiates the antitumor effects of bortezomib in multiple myeloma cells by inhibiting the mTOR/NF-κB signal pathway

“…PLD1 is known to participate in several cellular physical functions such as vesicular transport, endocytosis, cell cycle progression, and T cell receptor-mediated primary and secondary immune responses [7][8][9]. It is also implicated in a variety of human diseases ranging from viral infections to neurodegeneration and cancer [10][11][12]. PLD1 is highly expressed in multiple tumors including breast, colorectal, glioma, and prostate cancers [13].…”